The mammary gland is a complex organ whose growth and development are controlled by the interaction of a wide variety of hormones and growth factors. These same factors play fundamental roles in the etiology and progression of the cancerous state. The first event in the action of these hormones and growth factors is the interaction with specific cell associated receptors. The availability and activity of each class of receptor is regulated by the ligand which it recognizes as well as the general hormonal/growth factor milieu of the target cell. Our emphasis has been on the interactions of prolactin (Prl), thyroid hormone, and estrogens with recent work also examining how epidermal growth factor (EGF), and EGF-like growth factors are affected by the interplay of these three classical hormones. In addition, we have explored the relationship of a membrane associated antilactogen binding site (ALBS) to the lactogenic hormone receptor on human breast cancer cell growth in culture. Lobulo-alveolar development of the mammary gland requires the priming action of both estrogen and progesterone to induce EGF receptors and production of EGF-like growth factors. In concert with insulin, Prl and glucocorticoids, EGF or alpha-TGF can promote full lobulo-alveolar development in vitro. This effect is not inhibited by beta-TGF. The primed mammary gland is more sensitive to alpha-TGF than to EGF. Prl induced growth of the mouse mammary epithelial cell NOG-8 appears to involve activation of protein kinase C (PKC). Prl induces translocation of the PKC from cytosol to the membranes within 10 min. of exposure to the hormone. Prl induced growth of human breast cancer cells can be blocked by non-steroidal antiestrogens such as tamoxifen. This action is through the ALBS which may be intimately associated with the Prl receptor. The antiprolactin action of tamoxifen, working through the ALBS, may have important clinical implications.